The plasma membrane components and cytoplasmic organelles of human lymphocytes and monocytes will be studied by freeze fracture and etching and thin section electron microscopy. Freeze etching combined with ferritin labelled antibody and KLH-anti-KLH complexes will be used to study the relationships between receptors and intramembranous particles. Using murine cell lines as a model, plasma membrane receptors for the Fc portion of IgG will be characterized. The topochemistry, modulation and genetic regulation of Fc receptors will be studied. Plasma membrane morphology and receptor activity will be related to certain in vitro functions, including cytoplasmic spreading, antibody dependent cell-mediated cytotoxicity (ADCC) and chemotaxis. We shall also investigate subpopulations of normal and abnormal human peripheral blood B and T cells and monocytes with respect to plasma membrane receptors, topography, modulation, and function. We shall combine immunoelectron microscopic techniques with biochemical and pharmacologic probes and cloning techniques in an effort to characterize these plasma membrane components. The proposal has broad implications relevant to characterization of cells involved in the normal and abnormal immune response, cell-cell interactions and the pathophysiology of diseases associated with primary and acquired immunologic deficiencies and neoplastic disease.